The purpose of this proposal is to further investigate the proteins (structural and histones) which are found in the polyoma virion and to determine their respective role(s) in viral infection, virion assembly, and cell transformation. The unique aspects of our proposed investigation include: 1. To determine the structural association and affinity of the various polypeptides (V1-7) associated with the DNA found in purified virions; and to determine what effects (i.e. regulatory) the isolated capsomeres and isolated polypeptides might have on cellular and viral macromolecular synthesis and on possible involvement in cell transformation. 2. Temperature sensitive (ts) mutants of polyoma will be used to investigate DNA-protein complexes isolated from infected cells at permissive and non-permissive temperatures. Biophysical polypeptide composition of the purified polyoma ts virions will also be determined. 3. The fate of the "input" polyoma core complexes from infected cells. This study may shed light on the mechanism of intracellular uncoating and possible involvement of virion polypeptides and histones in the expression of early and late viral functions. 4. Determination of the existence or absence of a repressor (like) substance in polyoma transformed cells which prevents the expression of the viral genome. These experiments will utilize both in vivo and in vitro systems to determine if viral synthesis can be interrupted. BIBLIOGRAPIC REFERENCES: McMillen, J., Center, M.S. and Consigli, R.A. 1976. Studies on the origin of the polyoma virus associated endonuclease. J. Virol. in press. Yeh, W.S., McGuire, M., Center, M.S. and Consigli, R.A. 1976. Partial purification and properties of a DNA-binding protein from nuclei of cells infected with polyoma virus. Biochim. et Biophys. Acta in press.